Over the last several years it has become apparent that the neurotransmitter serotonin (5-hydroxytryptamine--5-HT) is associated directly or indirectly with a number of physiological phenomena, including appetite, memory, thermoregulation, sleep, sexual behavior, anxiety, depression, and hallucogenic behavior [Glennon, R. A., J. Med. Chem. 30, 1 (1987)].
It has been recognized that-there are multiple types of 5-HT receptors. These receptors have been classified as 5-HT.sub.1, 5-HT.sub.2, and 5-HT.sub.3 receptors, with the former being further divided into the sub-classes 5-HT.sub.1A, 5-HT.sub.1B, 5-HT.sub.1C, and 5-HT.sub.1D.
Selected 2-amino-1,2,3,4-tetrahydronaphthalenes (2-aminotetralins) and 3-aminochromanes have been shown to exhibit binding affinity at the 5-HT.sub.1A receptor.
A application Ser. No. 315,750 filed Feb. 27, 1989, refiled and now U.S. Pat. No. 5,389,687, describes certain 2-aminotetralins substituted in the 8-position by formyl, cyano, halo, hydroxymethyl, carboxamido, carboxyl, or alkoxycarbonyl. The compounds are described as exhibiting high binding affinity at the 5-HT.sub.1A receptor. 2-aminotetralins in which the 8-position is substituted by, among others, formyl, are also described in EPO patent application No. 272,534. In addition, application Ser. No. 315,752 filed Feb. 27, 1989, refiled and now U.S. Pat. No. 5,389,687, describes other 2-aminotetralins substituted in the 8-position and 3-aminochromanes substituted in the 5-position by sulfides, sulfoxides, and sulfones. These compounds, as well, are described as having binding affinity at the 5-HT.sub.1A receptor.
Another class of 2-aminotetralins are described in European Patent Application No. 343,830, published Nov. 29, 1989. These compounds have a piperazinyl or homopiperazinyl moiety in the 2-position and, distinct from the foregoing tetralins, do not exhibit affinity for serotonin receptors but rather inhibit the re-uptake of serotonin. We have now discovered a further class of compounds which, by reason of their 5-HT.sub.1A agonist activity, are useful in the treatment, for example, of sexual dysfunction, anxiety, depression, obsessive-compulsive behavior, cognition disorders, emesis, drug abuse, hypertension, excess acid secretion, and eating disorders, such as anorexia.